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Characterization of the human neutrophil alloantigen-3a

Abstract

Transfusion-related acute lung injury (TRALI) is a frequent cause of transfusion-associated morbidity and mortality. Severe TRALI is often due to antibodies in blood components directed against the human neutrophil alloantigen-3a (HNA-3a). We show here that the HNA-3a antigen arises from a nucleotide polymorphism in the choline transporter-like protein-2 gene (SLC44A2), with the resulting variation at amino acid position 154 determining the reactivity of the protein with HNA-3a–specific antibodies; the variant with an arginine at this position, rather than a glutamine, constitutes the HNA-3a antigen. The molecular identification of this antigen should facilitate the development of assays for blood donor screening to lower the risk of TRALI.

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Figure 1: Reactivity of antibodies specific for HNA-3a.

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Acknowledgements

We thank A. Teumer for running the data analysis of the Study on Health in Pomerania for population-wide gene frequency analysis of the HNA-3a–encoding polymorphism. We highly appreciate the expertise and support of J. Hoppen and H. Hippe (Chromatec) for expression of recombinant protein fragments. We thank T.E. Warkentin for valuable discussion and suggestions. This work was supported by an unrestricted grant of the Deutsche Rote Kreuz-Blutspendedienst West, Hagen, Germany; by the Land Mecklenburg-Vorpommern, Exzellenzinitiative UG 07-064; by the Bundesministerium für Bildung und Forschung, Zentrum für Innovationskompetenz Humorale Immunreaktionen bei Herz-Kreislauf Erkrankungen (ZIK-HIKE) 03Z2CK1 and 03Z2CI1 and Zentrum für Innovationskompetenz Funktionelle Genomforschung (ZIK FunGene 03ZIK331).

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Authors

Contributions

A.G. designed the study, supervised the experiments, evaluated the results and wrote the manuscript. J.W. performed the immunoprecipitation studies, evaluated the experiments and wrote the manuscript. E.H. and U.V. performed the mass spectrometry experiments, characterized the protein and wrote the manuscript. B.F. affinity-purified the antibodies and performed the flow cytometry and chemiluminescence experiments. A.R. and J.B. contributed the human antibodies, characterized the granulocytes serologically, developed the sequence-specific PCR method, performed all granulocyte aggregation tests and wrote the manuscript. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Andreas Greinacher.

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The Deutsche Rote Kreuz Blutspendedienst West Hagen and the University Greifswald submitted a patent application to the Deutsche Patent und Markenamt to use the HNA-31 epitope for screening of blood donors.

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Supplementary Figure 1, Supplementary Table 1 and Supplementary Methods (PDF 423 kb)

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Greinacher, A., Wesche, J., Hammer, E. et al. Characterization of the human neutrophil alloantigen-3a. Nat Med 16, 45–48 (2010). https://doi.org/10.1038/nm.2070

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